eMedicine Specialties > Endocrinology > Thyroid

Goiter, Diffuse Toxic: Differential Diagnoses & Workup

Author: Bernard Corenblum, MD, FRCP(C), Professor of Medicine, Director, Endocrine-Metabolic Testing and Treatment Unit, Ovulation Induction Program, Department of Internal Medicine, Division of Endocrinology, University of Calgary, Canada
Coauthor(s): Oluyinka S Adediji, MD, Consulting Staff, Department of Adult and General Medicine, Health Services Incorporated, Montgomery, Alabama; Paul Killian, MD, Former Chief of Endocrine Service, Former Associate Professor, Department of Internal Medicine, Harlem Hospital, Harlem Hospital Center
Contributor Information and Disclosures

Updated: Jun 4, 2009

Differential Diagnoses

Other Problems to Be Considered

If an associated ophthalmopathy is present, the diagnosis of diffuse toxic goiter is obvious.

Other common causes of hyperthyroidism include various forms of thyroiditis, hyperfunctioning (hot) nodule, multinodular goiter, iatrogenic (thyroxin and/or triiodothyronine ingestion). Iodine administration, such as drugs or contrast media, may precipitate hyperthyroidism in underlying nodular thyroid disease. Palpation of the thyroid gland gives useful clinical information in the separation of these entities.

Rare causes include TSH-secreting pituitary tumors, ectopic thyroxin production (struma ovarii), human chorionic gonadotropin (HCG) hypersecretion (trophoblastic disease, ectopic secretion), exogenous source (eg, hamburger thyrotoxicosis), and malingering (thyroxin ingestion). Peripheral resistance to thyroid hormone (receptor defect) may result in a complicated similar clinical picture. 

Anxiety/psychotic state, pheochromocytoma, pregnancy and hyperemesis gravidarum, menopause, carcinoid syndrome, cocaine and other drug use

Primary systemic or organ diseases, such as atrial fibrillation, weight loss, or myopathy, require hyperthyroidism to be considered as an underlying cause.

Workup

Laboratory Studies

• If hyperthyroidism due to diffuse toxic goiter is suspected after history and physical examination, the following should be performed:
  • Serum TSH (sensitive or third-generation assay): Levels suppressed below normal indicate the need for more tests. Normal serum TSH level rules out this diagnosis.
  • Serum free thyroxin (T4), or equivalent test, that compensates for any changes in thyroid-binding globulin. If levels are elevated, then hyperthyroidism is diagnosed. Levels will be in the normal range in about 5% of cases.
  • If free thyroxin is normal, then obtain total or free serum triiodothyronine (T3) level. If levels are elevated, then hyperthyroidism is diagnosed. If levels are normal, then subclinical hyperthyroidism is present.
  • The presence of ophthalmopathy indicates the diagnosis, and no more diagnostic testing is needed regarding the cause of the hyperthyroidism.
  • Serum anti-TSH receptor antibodies measurements can be obtained. These antibodies are present in more than 90% of cases of diffuse toxic goiter, depending on the assay.
  • An alternative test is radioiodine uptake. It will separate diffuse toxic goiter (elevated or normal uptake) from the hyperthyroid phase of thyroiditis (suppressed uptake). If the hyperthyroid symptoms have been present for more than 4 months, then thyroiditis is not the cause. This test is contraindicated in women who are pregnant or breastfeeding.
  • An elevated or normal uptake may be found with a single nodular goiter and a multinodular goiter. These may be separated from diffuse toxic goiter by the absence of anti-TSH receptor antibodies, clinical examination, or thyroid scan (technetium-99m or I-123) or ultrasonography.
  • Concomitant presence of Hashimoto thyroiditis may be detected by serum antithyroid antibodies (anti-TPO or thyroperoxidase).
  • If confirmation of oculopathy is needed, then orbital CT or MRI may be performed.
• Diffuse toxic goiter would have a suppressed serum TSH level, elevated serum free thyroxin level (or T3 if needed), elevated titer of anti-TSH receptor antibodies, or elevated radioiodine uptake. No further testing is needed.
• Consideration of complications: ECG should be performed if arrhythmia is suspected; liver function tests may be indicated.
• Consideration of associated disorders: If clinical suspicion, screen for adrenal insufficiency, type 1 diabetes, gonadal failure, other autoimmune disease (eg, pernicious anemia, rheumatoid arthritis, immune thrombocytopenic purpura). Concomitant Hashimoto thyroiditis may have an effect on spontaneous resolution or progression to a hypothyroid state.
• Drugs that may alter T4 laboratory results include anabolic steroids, androgens, estrogens, heparin, iodine, phenytoin, rifampin, salicylates, and thyroxine/triiodothyronine.

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